AZ: Structure-based design, led to osimertinib. Covalent target Cys797, mutant-selective profile #MAP16
8:24am September 23rd 2016 via Hootsuite
AZ: 60% of TKI resist is T790M; 2nd gen irreversible EGFR inhib then developed (afatinib, dacomitinib). Effectiveness limited #MAP16
8:23am September 23rd 2016 via Hootsuite
AstraZeneca talk (name?) '95 Gefitinib (IRESSA) theh first EGFR TKI' high response to Exon 19, L858R mutations #MAP16
8:19am September 23rd 2016 via Hootsuite
Lord: '13 Nature Med ref https://t.co/iJ7WNqLd9C With PARPi, secondary resist clones can be targeted (Wee1) #MAP16
8:13am September 23rd 2016 via Hootsuite
Lord: Lays out the synthetic lethality paradigm; from observation of drug resistance via a partner #MAP16
8:11am September 23rd 2016 via Hootsuite
Lord: Dev of PARP inh - potent, small-molecule, selectively targeting defective BRCA1/2 https://t.co/AIdmV5Fv6R KuDOS now AZ #MAP16
8:09am September 23rd 2016 via Hootsuite
Lord: a 'holy trinity': the biomarker, its penetrance, mol mechanism; heterogeneity, plasticity, evol; and optimal combinations #MAP16
8:07am September 23rd 2016 via Hootsuite
Lord (ICR UK) at AstraZeneca-sponsored luncheon: '10 BMC Ref https://t.co/UOWQUz99TH ~750 entities, 250 genes, 1% of the genome #MAP16
8:05am September 23rd 2016 via Hootsuite
Singh: Concludes w/Globe and Mail - In Canada, hockey is to sport as stem cells is to science https://t.co/3MLeRSSnuc #MAP16
7:51am September 23rd 2016 via Hootsuite
Singh: (Patients, after relapse, are often palliated, no re-examination of the mutations.) Found similar char's in spinal mets #MAP16
7:42am September 23rd 2016 via Hootsuite
Singh: Treat mice with radiation, Rx; mice have MRD and recur. GFP-labelled cells can be re-harvested, interrogated for met mutations #MAP16
7:41am September 23rd 2016 via Hootsuite
Singh: Targeting Bmi1 w/ PTC Therapeutics; showed data on promise of this approach. MB - sampled only once. Moving to NOD-SCID mice #MAP16
7:39am September 23rd 2016 via Hootsuite
Singh: Stem cells - is it Dorian Gray or Benjamin Button? '09 ref https://t.co/2MZUe5X8IG Impt in type 3 MB. Bmi1 gene reg by Sonic #MAP16
7:30am September 23rd 2016 via Hootsuite
Singh: The 4 subtypes published '12 ref https://t.co/yqnfJtrc8x Shh signaling: drives development, and disregulated, drives MB #MAP16
7:27am September 23rd 2016 via Hootsuite
Singh: Hisopathological subtypes 'are of minimal prognostic utility'; different groups characterize them, published '12 #MAP16
7:25am September 23rd 2016 via Hootsuite
Singh: Cushing, Bailey in the '20's. From 50% to now 80% 5y survivorship for std-risk pts. But survivors have neuro damage #MAP16
7:23am September 23rd 2016 via Hootsuite
Singh: One pt died at 15mo, another alive 8y later. But appeared identical. Cancer is like a river 'one cannot step twice' in it #MAP16
7:22am September 23rd 2016 via Hootsuite
Singh: Introduces herself as a neurosurgeon, using medulloblastoma. Starts w/2 childhood cases, most common ped brain tumor #MAP16
7:20am September 23rd 2016 via Hootsuite
Sheila Singh (McMaster Univ Ontario Canada) Therapeutic targeting of childhood medulloblastoma - strategies for blocking recurrence #MAP16
7:19am September 23rd 2016 via Hootsuite
Attard: Presents data from this '15 STM ref https://t.co/hZrLixTrRZ Poster here at #MAP16 develops a ddPCR assay for AR
7:14am September 23rd 2016 via Hootsuite
Attard: Showed results of wt AR vs mutant AR (L702H) over treatment; AR alleles don't acquire CNAs. https://t.co/atikTX0Rg3 #MAP16
7:13am September 23rd 2016 via Hootsuite
Attard: Uses this approach w/genotypes for monoallelic dels '14 ref https://t.co/fybeUCTAEJ #MAP16
7:02am September 23rd 2016 via Hootsuite
Attard: Chose 3 - mono-allelelic dels in 21q22, 8p21 (NKX3.1) and 10q22 (PTEN); pt muts in other genes #MAP16
6:59am September 23rd 2016 via Hootsuite
Attard: Discusses difficulty of CTC analysis in early-stage pts. Pre-analytic steps impt; ctDNA goes up in advanced disease #MAP16
6:58am September 23rd 2016 via Hootsuite
Attard: Use sequentially-collected plasma samples associated w/treatment resistance, only 6ng input. #MAP16
6:56am September 23rd 2016 via Hootsuite
Attard: mCRPC - after first-line castration, castration resistant prostate cancer. Hypothesis - sub-clonal muts that emerge #MAP16
6:55am September 23rd 2016 via Hootsuite
Gerhardt Attard (CRUK): Plasma AR analysis to direct the management of metastatic CRPC (PARADIGM) #MAP16
6:53am September 23rd 2016 via Hootsuite
Vanhaesebroeck: Q's: PI3Kdelta inh immunosupp but also heighten immune resp - but what dose? which cancers? What combinatios? #MAP16
6:48am September 23rd 2016 via Hootsuite
Vanhaesebroeck: PI3Kinh often leads to colitis; freq of AE, behaves like an immune modulator. Pneumonits, coiis, rash, inflam #MAP16
6:42am September 23rd 2016 via Hootsuite
Vanhaesebroeck: Immunology connection - PI3Kd inh blocks solid tumor; can a leukemia drug be used? Balance bet Treg, Th, CTL Killer #MAP16
6:40am September 23rd 2016 via Hootsuite
Vanhaesebroeck: When inhibited in malignant niche - go into circ, no direct cytotox, do not get stim back in lymph node #MAP16
6:36am September 23rd 2016 via Hootsuite
Vanhaesebroeck: CLL cells in-vitro - no direct cytotox. Showed delta is impt for signaling downstream. #MAP16
6:35am September 23rd 2016 via Hootsuite
Vanhaesebroeck For CLL, FL, SLL: in CLL have lymph node accumulation; Post-treatment, moves to circulation #MAP16
6:33am September 23rd 2016 via Hootsuite
Vanhaesebroeck: Delta: K Okkenhaug generated kinase-dead p110delta mice - reviews drugs developed as a result. ICOS Zydelig #MAP16
6:32am September 23rd 2016 via Hootsuite
Vanhaesebroeck: He cloned it in '97 (PNAS); mainly in leukocytes. alpha form amplified/mut in cancer. delta: immune, inflamm disease #MAP16
6:30am September 23rd 2016 via Hootsuite
Vanhaesebroeck: Cells can live w/only 5% PI3K activity; dev of resistance common. Combination Rx will be req'd. 1 Drug - p110delta #MAP16
6:29am September 23rd 2016 via Hootsuite
Vanhaesebroeck: Feels PI3K has been over-simplified; PIK3CA very freq in some ca's. PTEN opposite direction. PI3Kinh thus far modest #MAP16
6:28am September 23rd 2016 via Hootsuite
Vanhaesebroeck: PI 3-kinase is a family of enzymes, 3 classes; Clas I acts downstream of Tyr Kinases, GPCRs, GTPases #MAP16
6:26am September 23rd 2016 via Hootsuite
Bart Vanhaesebroeck (UCL London UK): PI3Kdelta a new kid on the block in cancer immunotherapy #MAP16
6:25am September 23rd 2016 via Hootsuite
Q: Failures? Sofia: What do you do about actionability? Br ca, lung have many Rx's; colorectal, other types is hard. #MAP16
5:52am September 23rd 2016 via Hootsuite
Q: (to Soria) Transloc vs ampl.? A: Poweful with transloc w/FGFR, not w/amplifications. Looking at interplay w/immunoRx #MAP16
5:47am September 23rd 2016 via Hootsuite
Paskorz: conclude that best Ab was DO-7 (DAKO) Ab on Leica Bond Max; cytoplasmic stain assoc'd w/TP53 LOF mutations #MAP16
5:44am September 23rd 2016 via Hootsuite
Paskorz: Cp 3 different ICH assays; devl. scoring for overexpr, complete absence; then cytoplasmic. Charted mut by IHC type #MAP16
5:41am September 23rd 2016 via Hootsuite
A lightning talk: Anna Paskorz (CURK) Opt p53 immunohistochemistry in HGSOC; 3 drugs in clinical trials (APR-246; Wee-1 inh AZD-1775) #MAP16
5:39am September 23rd 2016 via Hootsuite
Calvo: Feels that with WES/WGS, and ImmunoRx targets; improve drug coverage, more biomarkers, improve data analysis and outcomes #MAP16
5:31am September 23rd 2016 via Hootsuite
Calvo: Of 100 ca pts: 60% can ID driver; 50% can treat (now 30 of the 100); 50% will respond (15/100); 50% sustainable (7/100) #MAP16
5:29am September 23rd 2016 via Hootsuite
Calvo: Concl w/precision medicine limitations - ORR 50-80% (not universal); limited duration of effectiveness, with resistance #MAP16
5:28am September 23rd 2016 via Hootsuite
Calvo: Shows slide of 10 projects just in EU - for BrCa, Renal, HCC, Ewing, early Pr Ca. Outcomes listed - ID targets, mechanisms #MAP16
5:24am September 23rd 2016 via Hootsuite
Calvo: PCAWG - PancCancer Analysis of Whole Genomes; 2600 WGS T/N pairs is the goal. #MAP16
5:22am September 23rd 2016 via Hootsuite
Calvo: Showed a huge slide, worldwide, listing dozens of ICGC projecs. From Mexico, to Singapore, to Saudi Arabia, many others #MAP16
5:21am September 23rd 2016 via Hootsuite
